Widespread deoxygenation of temperate lakes.

The concentration of dissolved oxygen in aquatic systems helps to regulate biodiversity1,2, nutrient biogeochemistry3, greenhouse gas emissions4, and the quality of drinking water5. The long-term declines in dissolved oxygen concentrations in coastal and ocean waters have been linked to climate warming and human activity6,7, but little is known about the changes in dissolved oxygen concentrations in lakes. Although the solubility of dissolved oxygen decreases with increasing water temperatures, long-term lake trajectories are difficult to predict. Oxygen losses in warming lakes may be amplified by enhanced decomposition and stronger thermal stratification8,9 or oxygen may increase as a result of enhanced primary production10. Here we analyse a combined total of 45,148 dissolved oxygen and temperature profiles and calculate trends for 393 temperate lakes that span 1941 to 2017. We find that a decline in dissolved oxygen is widespread in surface and deep-water habitats. The decline in surface waters is primarily associated with reduced solubility under warmer water temperatures, although dissolved oxygen in surface waters increased in a subset of highly productive warming lakes, probably owing to increasing production of phytoplankton. By contrast, the decline in deep waters is associated with stronger thermal stratification and loss of water clarity, but not with changes in gas solubility. Our results suggest that climate change and declining water clarity have altered the physical and chemical environment of lakes. Declines in dissolved oxygen in freshwater are 2.75 to 9.3 times greater than observed in the world's oceans6,7 and could threaten essential lake ecosystem services2,3,5,11.

Enantiomeric separation of nefopam and cathinone derivatives using a supramolecular deep eutectic solvent as a chiral selector in capillary electrophoresis.

The present study investigates the utilization of a supramolecular deep eutectic solvent (SUPRADES), consisting of sulfated-ß-cyclodextrin (S-ß-CD) and citric acid (CA), as a chiral selector (CS) in capillary electrophoresis for the enantiomeric separation of nefopam (NEF) and five cathinone derivatives (3-methylmethcathinone [3-MMC], 4-methylmethcathinone [4-MMC], 3,4-dimethylmethcathinone [3,4-DMMC], 4-methylethcathinone [4-MEC], and 3,4-methylendioxycathinone [MDMC]). A significant improvement in enantiomeric separation of the target analytes was observed upon the addition of S-ß-CD-CA to the background electrolyte (BGE), leading to a baseline separation of all analytes. In particular, the optimum percentage of S-ß-CD-CA, added to the BGE, was determined to be 0.075% v/v for NEF (Rs = 1.5) and 0.050% v/v for three out of five cathinone derivatives (Rs = 1.5, 1.6, and 2.4 for 3-MMC, 4-MEC, and 3,4-DMMC, respectively). In the case of 4-MMC and MDMC, a higher percentage of the CS, equal to 0.075% and 0.10% v/v, respectively, was required to achieve baseline separation (Rs = 1.5, 1.9 for MDMC and 4-MMC, respectively). The outcomes of the present study highlight the potential effectiveness of using SUPRADES as a CS in electrophoretic enantioseparations.

Exploring a Lux® i-Amylose-3 column in normal phase and polar-organic mode for chiral separation of cathinone derivatives and pyrovalerones using high-performance liquid chromatography.

Each year, new psychoactive substances appear on the global drug market leading to constant changes. Most of these compounds with stimulating effect possess a chiral center, thus leading to two enantiomers with presumably different pharmacological properties. Among them, synthetic cathinones, often misleadingly traded as "bath salts," play an important role. There is little knowledge about the distinct effect of the enantiomers. The aim of this study was to test a commercially available Lux® i-Amylose-3 column by HPLC-UV for enantiorecognition of cathinone derivatives. Overall, 80 compounds were tested in normal phase mode, where 75 substances were separated under initial conditions. After method optimization, at least partial separation was achieved for the remaining compounds. The same set of substances was measured in polar-organic mode, where 63 analytes were resolved into their enantiomers under initial conditions with very short retention times. Both modes showed complementary results for the individual compounds. Furthermore, the tested methods proved to be suitable for differentiation of positional isomers, which can be useful for drug checking programs. All measurements were carried out under isocratic conditions, and intraday and interday repeatability tests were performed.

Screening of Astec® CHIRALDEX™ G-PN and LIPODEX™ D gas chromatography columns for enantioseparation of amphetamine derivatives.

Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class. Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® Chiraldex™ G-PN column containing 2,6-di-O-pentyl-3-propionyl-γ-cyclodextrin and a Lipodex™ D column containing heptakis-(2,6-di-O-pentyl-O-acetyl)-ß-cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS-QP2010 SE system. Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility.1 As a result, 35 amphetamines were tested as their TFAA-derivatives. A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the Chiraldex™ G-PN column. Six baseline and nine partial separations were observed with the Lipodex™ D column, respectively.

Enhancing interprofessional collaboration in paediatric training: Insights from profession-specific experiences and implications for future education.

AIM: There is limited evidence on trainees' and instructors' needs and perspectives concerning interprofessional simulation-based trainings. We aimed to study task distribution among team members, profession-specific learning effects and enhancing collaboration and competencies within medical teams. METHODS: This prospective study examined expectations and experiences of medical and nursing students during paediatric emergency training in a tertiary care centre with questionnaires before and after a training. Further, expert interviews were conducted to identify the needs for interprofessional training. Results were used to design a standardised checklist for structured preparation of interprofessional paediatric emergency management training. RESULTS: Of the nursing students, 82% initially intended to assume the role of the team leader, but only 5.8% did so during training. Both professions emphasised the significance of effective communication and transparent task distribution for successful collaboration. Experts highlighted the importance of proficiency in basic technical skills and identified non-technical skills such as closed-loop communication and the 10-4-10 principle as crucial for both professions. CONCLUSION: The study revealed profession-specific variations in the intention of acquiring the team leader or member role. Interprofessional training emerges as a potential strategy to dismantle these structures and promote shared responsibilities. The checklist aims to facilitate structured preparation of a training.

Unaccounted CO2 leaks downstream of a large tropical hydroelectric reservoir.

Recent studies show that tropical hydroelectric reservoirs may be responsible for substantial greenhouse gas emissions to the atmosphere, yet emissions from the surface of released water downstream of the dam are poorly characterized if not neglected entirely from most assessments. We found that carbon dioxide (CO2) emission downstream of Kariba Dam (southern Africa) varied widely over different timescales and that accounting for downstream emissions and their fluctuations is critically important to the reservoir carbon budget. Seasonal variation was driven by reservoir stratification and the accumulation of CO2 in hypolimnetic waters, while subdaily variation was driven by hydropeaking events caused by dam operation in response to daily electricity demand. This "carbopeaking" resulted in hourly variations of CO2 emission up to 200% during stratification. Failing to account for seasonal or subdaily variations in downstream carbon emissions could lead to errors of up to 90% when estimating the reservoir's annual emissions. These results demonstrate the critical need to include both limnological seasonality and dam operation at subdaily time steps in the assessment of carbon budgeting of reservoirs and carbon cycling along the aquatic continuum.

Patient-Reported Outcome Measures (PROMs) with Refractive and Diffractive Extended Depth of Focus (EDOF) Intraocular Lenses.

BACKGROUND: Extended depth of focus intraocular lenses (EDOF-IOLs) provide unaided far- and mid-range vision. Refractive IOLs, in contrast to diffractive designs, are associated with a lower depth of focus and absence of dysphotopsia. The aim of this study was to assess spectacle independence for far-range, mid-range, and near-vision activities in patients after implantation of refractive or diffractive EDOF-IOLs using patient-reported outcome measures (PROMs) in a real-world setting. PATIENTS AND METHODS: In 2021 and 2022, all patients in a single center referred for bilateral cataract surgery were assigned to 7 experienced cataract surgeons who either bilaterally implanted only a diffractive EDOF-IOL (Carl Zeiss Meditec AG, AT LARA Jena, Germany, three surgeons) or refractive EDOF-IOL (Johnson & Johnson Vision Inc., Tecnis Eyhance Irvine, California, USA, four surgeons) at the surgeon's discretion, with the aim of bilateral emmetropia. Six months after both cataract surgeries, all patients were contacted by telephone and asked to report their outcomes using a structured questionnaire investigating their spectacle usage for various daily activities and their experience with night glare or halos. Inclusion criteria were a normal postoperative visual potential based on the preoperative examination and completion of the questionnaire regarding postoperative visual experience. RESULTS: Of the patients, 514 underwent bilateral cataract surgery aiming for bilateral emmetropia with the implantation of EDOF-IOLs (422 with Tecnis Eyhance and 92 with AT LARA). A complete questionnaire was obtained from 472 (92%) patients, who were included in the study (393 vs. 79). Comparing Tecnis Eyhance with AT LARA IOL, 54 vs. 57% patients were able to perform most of their daily activities without spectacles, 9 vs. 19% reported not being dependent on spectacles at all, 25 vs. 29% reported using their smartphones without spectacles, 15 vs. 49% patients reported experiencing glares or halos at night, and 1 vs.15% with driving disturbance. Overall, 95 vs. 93% patients described themselves as "satisfied" or "highly satisfied" with their IOL. CONCLUSIONS: With both types of EDOF-IOLs, the majority of patients could perform most of their daily activities without spectacles, except reading, and were highly satisfied with their IOLs. Patients with diffractive Zeiss AT LARA EDOF-IOLs were more likely to accomplish unaided near-range visual tasks; however, they were also at a higher risk of experiencing glares or halos at night.

The Enantioselective Potential of NicoShell and TeicoShell Columns for Basic Pharmaceuticals and Forensic Drugs in Sub/Supercritical Fluid Chromatography.

The enantioselective potential of two macrocyclic glycopeptide-based chiral stationary phases for analysis of 28 structurally diverse biologically active compounds such as derivatives of pyrovalerone, ketamine, cathinone, and other representatives of psychostimulants and antidepressants was evaluated in sub/supercritical fluid chromatography. The chiral selectors immobilized on 2.7 µm superficially porous particles were teicoplanin (TeicoShell column) and modified macrocyclic glycopeptide (NicoShell column). The influence of the organic modifier and different mobile phase additives on the retention and enantioresolution were investigated. The obtained results confirmed that the mobile phase additives, especially water as a single additive or in combination with basic and acidic additives, improve peak shape and enhance enantioresolution. In addition, the effect of temperature was evaluated to optimize the enantioseparation process. Both columns exhibited comparable enantioselectivity, approximately 90% of the compounds tested were enantioseparated, and 30% out of them were baseline enantioresolved under the tested conditions. The complementary enantioselectivity of the macrocyclic glycopeptide-based chiral stationary phases was emphasized. This work can be useful for the method development for the enantioseparation of basic biologically active compounds of interest.

Use of Spectacles after Cataract Surgery.

PURPOSE: The goal of this study was to investigate the use of spectacles in everyday life after bilateral cataract surgery with a preoperative refractive target of emmetropia in both eyes. In addition, we analyzed the total cost of spectacles and the patient's visual satisfaction at least 6 months after surgery. METHODS: Patients after bilateral cataract surgery with implantation of an aspheric monofocal IOL (Tecnis 1, Johnson & Johnson) with a preoperative refractive target of emmetropia in both eyes and a documented refractive outcome were included in this prospective observational study. In a phone interview ≥ 6 months after surgery, the following items were assessed: type of spectacles purchased and overall cost, type of activity with and duration of spectacle wear, and satisfaction with the visual situation. RESULTS: Seventy patients were included in this study. Depending on their postoperative refraction, patients were divided into group A (n = 27) with perfect emmetropia in both eyes (i.e., spherical equivalent [SE] of ≥ - 0.25 D to ≤ + 0.25 D), group B (n = 21) with achieved emmetropia in one eye (i.e., SE of ≥ - 0.25 D to ≤ + 0.25 D) and a myopic refraction in the other eye (< - 0.25 D), and group C (n = 22) with bilateral myopic results (SE of < - 0.25 D). Overall, 84% of patients had purchased new spectacles, mostly varifocals (59%) or reading glasses (24%) at the median cost of 980 Swiss Francs (mean: CHF 912 ± 746). Despite patients' initial reasoning for their lens choice to require reading glasses only, varifocal glasses were worn for more than 50% or all of awake time by 48% of patients in group A, 43% in group B, and 68% in group C. Despite their regular spectacles use, patients' visual satisfaction was very high in all three groups. CONCLUSIONS: Most patients who achieve perfect bilateral emmetropia after implantation of monofocal aspheric lenses buy varifocal spectacles within 6 months, and more than half of all patients use their varifocal spectacles for more than 50% of their awakening time. The costs for such spectacles are high.

Evaluation of cyclodextrin- and cyclofructan-based chiral selectors for the enantioseparation of psychoactive substances in capillary electrophoresis.

During this study, a simple and easy-to-prepare electrophoretic method was developed for the enantioseparation of amphetamine and cathinone derivatives. Different types of ß-cyclodextrin and cyclofructan-based chiral selectors (CSs), both native and derivatized, were utilized, and the most effective ones, in terms of resolution and analysis time, were identified. In addition, several electrophoretic parameters, such as background electrolyte concentration and pH, and CS concentration, were examined to optimize the separation conditions. Under the optimal electrophoretic conditions, 10 psychoactive substances were enantiomerically separated using 1 mM sulfated cyclofructan-6 (SCF-6) for the amphetamine derivatives and 1 mM sulfated cyclofructan-7 (SCF-7) for the cathinone derivatives dissolved in an aqueous solution of 20-mM monobasic sodium phosphate at pH 2.5, a temperature of 25°C, and an applied voltage of 25 kV. In addition, the method was validated by estimating the intra- and interday precision.

Bilateral blindness after uneventful brolucizumab injection for macular degeneration.

BACKGROUND: We report a very severe case of bilateral panuveitis and ischemic vasculitis with possible perineural inflammation, which followed bilateral intravitreal brolucizumab administration in a patient with neovascular age-related macular degeneration (nAMD). CASE PRESENTATION: On December 11, 2020, a 81-year-old woman presented with severe bilateral loss of vision. Eight days earlier, she had received uneventful bilateral injection of brolucizumab, a novel anti-vascular endothelial growth factor (VEGF) single-chain variable region (scFv) recombinant protein drug, for treatment of neovascular age-related macular degeneration (nAMD). Slit-lamp examination revealed signs of a bilateral panocular vasculitis with ischemia. Scanning laser ophthalmoscopy of her left eye revealed marked vascular sheathing. T1 fat-saturated post-contrast images of the orbit revealed a higher-than-normal signal of the choroid, with localized choroidal detachment. Additionally, pathologic enhancement was visible around the optic nerve in the orbit, which was interpreted as vasculitis. Due to the severe bilateral panuveitis with vasculitis, an additional vitreous tap was obtained, which revealed elevated levels of interleukin six and interleukin ten. CONCLUSIONS: To our knowledge, this is the first documented case showing both panuveitis and ischemic vasculitis with possible perineural inflammation. We do not recommend performing bilateral brolucizumab injections until more data is available regarding the mechanism of brolucizumab-induced vasculitis. From a clinical point of view, we find it difficult to justify the use of brolucizumab when there are other well-known agents, such as ranibizumab and aflibercept, which have better safety profiles and comparable efficacy.

Staff dose evaluation by application of radiation protection during endoscopic retrograde cholangiopancreatography (ERCP) procedures performed with a mobile C-arm.

BACKGROUND: The radiation dose to staff performing endoscopic retrograde cholangiopancreatography (ERCP) is not negligible. PURPOSE: To evaluate the shielding effect of a table-suspended lower-body radiation shield for the positions in the room occupied by the operator, assisting nurse, and anesthesiologist, used during ERCP procedures with a mobile C-arm. MATERIAL AND METHODS: Eye lens dose, whole body dose, and extremity dose were measured with and without a table-suspended lower-body radiation shield in a phantom model and in clinical routine work. The effect of the shield was evaluated for each scenario and compared, and a projection was made for when shielding should be required from a regulatory point of view. RESULTS: In the phantom measurements, the shield provided significant shielding effects on the body and lower extremities for the operator but no significant shielding of the eye lens. The shielding effect for the assisting nurse was limited to the lower extremity. The clinical measurements yielded the same general result as the phantom measurements, with the major difference that the shield provided no significant reduction in the whole-body dose to the operator. CONCLUSION: The table-suspended shield has a significant shielding effect for the lower extremities of the operator and assisting nurse. For annual dose-area product values >300,000 cGycm2, the protection of the operator should be reinforced with a ceiling-suspended shield to avoid doses to the eye lens and body in excess of regulatory dose restrictions.

Characterization of Three Novel 4-Methylaminorex Derivatives Applied as Designer Drugs.

The ongoing development of more and more new psychoactive substances continues to be a huge problem in 2022 affecting the European and international drug market. Through slight alterations in the structure of illicit drugs, a way to circumvent the law is created, as the created derivatives serve as legal alternatives with similar effects. A common way of structure modification is the induction of a halogen residue. Recently, halogenated derivatives of the well-known designer drug 4-methylaminorex appeared on the market and are available in various online shops. In this study, three novel halogenated 4-methylaminorex derivatives, namely 4'-fluoro-4-methylaminorex, 4'-chloro-4-methylaminorex, and 4'-bromo-4-methylaminorex, were purchased online and characterized using nuclear magnetic resonance (NMR) spectroscopy, liquid chromatography-high-resolution mass spectrometry (LC-HRMS), and chiral high-performance liquid chromatography with ultraviolet detection (HPLC-UV). These derivatives possess two stereogenic centers, and analyses revealed that all of them were present as a racemic mixture of the trans diastereomeric form.

Emergency Vitrectomies for Retinal Detachment Before and During the Coronavirus Pandemic - A Retrospective Single Centre Analysis.

BACKGROUND: While the corona pandemic and the resulting containment measures affect the number of elective surgical procedures, the impact on emergency surgical interventions is less tangible. This analysis quantifies the frequency of emergency vitrectomies for retinal detachment and investigates underlying factors. METHODS: Retrospective identification of patients who underwent primary emergency vitrectomies for retinal detachment at the Cantonal Hospital of Lucerne between 01.01.2018 - 31.12.2020. Parameters were collected, including demographics, date of hospitalisation, reported onset of symptoms, pre-operative best corrected visual acuity (BCVA), involvement of the macula, and canton of residence. RESULTS: Overall, a total of 665 patients with 683 eyes underwent emergency surgery for primary retinal detachment in the time span of 01.01.2018 - 31.12.2020. Median monthly number of surgeries was 20. During the first Swiss national lockdown (16.03.2020 - 19.04.2020), a minimum of 9 vitrectomies was recorded in March 2020. A maximum of 36 vitrectomies was conducted in August 2020. The mean age of patients was 61.5 years. Of the 665 patients, 133 (20.0%) were residents of the canton of Ticino. Median pre-operative BCVA was 0.25 over all three years, and no significant reduction in pre-operative BCVA was observed during or after the lockdown. The proportion of eyes with involvement of the macula was 52.2%. In 2018, this proportion (47.6%) was significantly lower than in 2019 and 2020 (Chi2 test, p < 0.001). However, cases with macular involvement in post lockdown months were not more frequent. Median time in days from reported symptom onset to hospitalisation was 5 days. In April 2020, the proportion of patients with > 14 days symptom duration was significantly higher (Chi2 test, p < 0.001). During the lockdown, there was a significant reduction in cases from Ticino. Also, patients from Ticino showed proportionally longer symptom duration after the lockdown. CONCLUSION: A significant reduction in the number of emergency vitrectomies was observed for the initial period of the coronavirus pandemic. Delayed emergency presentation is not assumed, since there was no increase in severity (i.e. macular involvement) or prolonged symptoms in the months following the lockdown. More protracted symptoms were only observed in patients from Ticino. The initial low numbers were generally made good later in the year.

Effect of Protective Measures on the Risk of SARS-CoV-2 Infection among Eye Clinic Staff Members.

BACKGROUND: Switzerland was strongly affected by the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that resulted in a nationwide lockdown in March 2020. Ophthalmologists were at most risk of contracting a SARS-CoV-2 infection due to their close working distance from patients. The aim of the study is to evaluate the overall effectiveness of protective measures on the risk of SARS-CoV-2 infection among employees in a large public eye hospital. MATERIAL AND METHODS: After lifting the lockdown in April 2020, standard precaution measures were taken, such as no handshaking and the use of operating face masks and a protective plastic shield on slit lamps and diagnostic devices. Only patients with no signs of SARS-CoV-2 disease were seen during the study period. Specific anti-SARS-CoV-2 IgG antibody titers were measured in eye clinic employees at the end of April 2020 (1st test phase) and in January 2021 (2nd test phase). The prevalence of SARS-CoV-2 IgG antibody titers among employees with daily patient contact was compared to staff members with no patient contact. RESULTS: The SARS-CoV-2 prevalence in employees with daily patient contact, with 0% in the 1st phase and 7.4% in the 2nd phase, was not significantly higher than the prevalence in the control group with no patient contact (0.9% in the 1st phase, p = 0.4; and 8.6% in the 2nd phase, p = 0.8). Furthermore, physicians were not at a significantly higher risk of SARS-CoV-2 infection compared to technicians, nurses, or office staff. CONCLUSIONS: This study shows that the abovementioned precaution measurements are effective in preventing transmission of SARS-CoV-2 infection in eye hospitals and enable us to resume practicing ophthalmology in a safe manner.

Successful use of a novel lux® i-Amylose-1 chiral column for enantioseparation of "legal highs" by HPLC.

Bath salts, fumigations, cleaners and air fresheners, behind these terms substances are hidden, which count as "Legal Highs". These fancy names are used to pretend Legal Highs as harmless compounds, to circumvent legal regulations for marketing as well as to increase the sales. Besides classic illicit drugs of synthetic origin such as amphetamines, cocaine and MDMA, the trade of these compounds, also known as new psychoactive substances (NPS), is not uncommon today. In many countries, NPS are still not subject to drug control. Among them, there are stimulants such as new amphetamine derivatives or cathinones, which possess a chiral centre. Little is known about the fact that the two possible enantiomers may differ in their pharmacological effect. The aim of this study was to test a novel HPLC column for the enantioseparation of a set of 112 NPS coming from different chemical groups and collected by internet purchases during the years 2010-2018. The CSP, namely Lux® 5 µm i-Amylose-1, LC Column 250 x 4.6 mm, was run in normal phase mode under isocratic conditions, UV detection was performed at 245 nm and 230 nm, injection volume was 10 µl and flow rate was 1 ml/min. With a mobile phase consisting of n-hexane/isopropanol/diethylamine (90:10:0.1), herein, 79 NPS were resolved into their enantiomers successfully, for 37 of them baseline resolution was achieved. After increase of lipophily of the mobile phase to 99:1:0.1, another 27 compounds were baseline separated. It was found that all separated NPS are traded as racemic compounds.

Determination of the chiral status of different novel psychoactive substance classes by capillary electrophoresis and ß-cyclodextrin derivatives.

Besides the abuse of well-known illicit drugs, consumers discovered new synthetic compounds with similar effects but minor alterations in their chemical structure. Originally, these so-called novel psychoactive substances (NPS) have been created to circumvent law of prosecution because of illicit drug abuse. During the past decade, such compounds came up in generations, the most popular compound was a synthetic cathinone derivative named mephedrone. Cathinones are structurally related to amphetamines; to date, more than 120 completely new derivatives have been synthesized and are traded via the Internet. Cathinones possess a chiral center; however, only little is known about the pharmacology of their enantiomers. However, NPS comprise further chiral compound classes such as amphetamine derivatives, ketamines, 2-(aminopropyl)benzofurans, and phenidines. In continuation of our project, a cheap and easy-to-perform chiral capillary zone electrophoresis method for enantioseparation of cathinones presented previously was extended to the aforementioned compound classes. Enantioresolution was achieved by simply adding native ß-cyclodextrin, acetyl-ß-cyclodextrin, 2-hydroxypropyl-ß-cyclodextrin, or carboxymethyl-ß-cyclodextrin as chiral selector additives to the background electrolyte. Fifty-one chiral NPS served as analytes mainly purchased from online vendors via the Internet. Using 10 mM of the aforementioned ß-cyclodextrins in a 10 mM sodium phosphate buffer (pH 2.5), overall, 50 of 51 NPS were resolved. However, chiral separation ability of the selectors differed depending on the analyte. Additionally, simultaneous enantioseparations, the determination of enantiomeric migration orders of selected analytes, and a repeatability study were performed successfully. It was proven that all separated NPS were traded as racemic mixtures.

Advantages and Pitfalls of Capillary Electrophoresis of Pharmaceutical Compounds and Their Enantiomers in Complex Samples: Comparison of Hydrodynamically Opened and Closed Systems.

Several research disciplines require fast, reliable and highly automated determination of pharmaceutically active compounds and their enantiomers in complex biological matrices. To address some of the challenges of Capillary Electrophoresis (CE), such as low concentration sensitivity and performance degradation linked to the adsorption and interference of matrix components, CE in a hydrodynamically closed system was evaluated using the model compounds Pindolol and Propranolol. Some established validation parameters such as repeatability of injection efficiency, resolution and sensitivity were used to assess its performance, and it was found to be broadly identical to that of hydrodynamically opened systems. While some reduction in separation efficiency was observed, this was mainly due to dispersion caused by injection and it had no impact on the ability to resolve enantiomers of model compounds even when spiked into complex biological matrix such as blood serum. An approximately 18- to 23-fold increase in concentration sensitivity due to the employment of wide bore capillaries was observed. This brings the sensitivity of CE to a level similar to that of liquid chromatography techniques. In addition to this benefit and unlike in hydrodynamically opened systems, suppression of electroosmotic flow, which is essential for hydrodynamically closed systems practically eliminates the matrix effects that are linked to protein adsorption.

Chiral separation of cathinone derivatives using ß-cyclodextrin-assisted capillary electrophoresis-Comparison of four different ß-cyclodextrin derivatives used as chiral selectors.

In the past decade, more than 100 different cathinone derivatives slopped over entire Europe due to their enormous popularity. Generally, these novel psychoactive substances are easily available via the internet. This fact leads to various social problems, since cathinones are substances with consciousness-changing effects and are mainly misused for recreational matters by their consumers. Cathinones possess a chiral center including two enantiomeric forms with potentially different pharmacological behavior. This fact makes analytical method development regarding their chiral separation indispensable. In this study, a chiral capillary zone electrophoresis method for the enantioseparation of 61 cathinone and pyrovalerone derivatives was developed by means of four different ß-cyclodextrin derivatives. As chiral selectors, native ß-cyclodextrin as well as three of its derivatives namely acetyl-ß-cyclodextrin, 2-hydroxypropyl-ß-cyclodextrin, and carboxymethyl-ß-cyclodextrin were used. The cathinone and pyrovalerone derivatives were either purchased in internet stores or seized by police. As a result, overall 58 of 61 studied substances were partially or baseline separated by at least one of the four chiral selectors using 10 mM of ß-cyclodextrin derivative in a 10 mM sodium phosphate buffer (pH 2.5). Furthermore, the method was found to be suitable for simultaneous enantioseparations, for enantiomeric purity checks and to differentiate between positional isomers. Moreover, an intra- and an interday validation was performed successfully for each chiral selector to prove the robustness of the method.

Comparison Between Interwoven Nitinol and Drug Eluting Stents for Endovascular Treatment of Femoropopliteal Artery Disease.

OBJECTIVES: Information on performance of different stent platforms in endovascular revascularisation of femoropopliteal lesions is controversial and scarce. METHODS: Interwoven nitinol (INS, Supera) were compared with drug eluting (DES, Zilver PTx) stents with primary intervention for femoropopliteal lesions. The primary endpoint was time to clinically driven target lesion revascularisation (CD-TLR) within 12 months. Secondary endpoints were time to death, amputation and composite of death, amputation and CD-TLR. Due to the retrospective analysis, inverse probability treatment weighted (IPTW) Cox models were calculated to reach more similar patient populations with weights for the average treatment effect of the population. The two sensitivity analyses were propensity score matching and adjustment for covariates. RESULTS: At 12 months, the cumulative incidence of CD-TLR in the INS group (13%) and DES group (18%) did not differ (HR 1.36, 95% CI 0.56-3.31). A significant interaction between stents used and grade of calcification was observed (p = .006). HR for CD-TLR was 6.4 (95% CI 1.3-32.5) in none to mildly calcified favouring INS, and 0.3 (95% CI 0.1-1.3) for moderate to severely calcified lesions favouring DES. Stent efficiency did not differ comparing treatment of popliteal lesions (HR 0.80; 95% CI 0.21-3.13). Sensitivity analyses confirmed the primary efficacy outcome for either adjusted (HR 1.16; 95% CI 0.51-2.62) or matched analysis (HR 1.35; 95% CI 0.50-3.62)). Interaction of stents with calcification grade was lost for adjusted (HR 0.28; 95% CI 0.06-1.19) and matched analysis (HR 0.53; 95% CI 0.10-2.91). CONCLUSION: Both stents (INS and DES) showed comparable results regarding CD-TLR in femoropopliteal lesions, so that one stent could not be favoured over the other, even for calcified or popliteal artery lesions.